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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H13FO2
Molecular Weight 244.2609
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TARENFLURBIL

SMILES

C[C@@H](C(O)=O)C1=CC(F)=C(C=C1)C2=CC=CC=C2

InChI

InChIKey=SYTBZMRGLBWNTM-SNVBAGLBSA-N
InChI=1S/C15H13FO2/c1-10(15(17)18)12-7-8-13(14(16)9-12)11-5-3-2-4-6-11/h2-10H,1H3,(H,17,18)/t10-/m1/s1

HIDE SMILES / InChI

Molecular Formula C15H13FO2
Molecular Weight 244.2609
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Tarenflurbil (Flurizan or R-flurbiprofen) is the single enantiomer of the racemate NSAID flurbiprofen. Tarenflurbil is a first in class, selective amyloid-beta42 (A42) lowering agent (SALA), which acts by modulating the activity of gamma-secretase, an enzyme that converts amyloid precursor protein to amyloid-beta. The reduction of A42 may prevent the development of the amyloid plaques thought to be a key pathological process associated with Alzheimer’s disease. For several years, research and trials for the drug were conducted by Myriad Genetics, to investigate its potential as a treatment for Alzheimer's disease. In a brief statement issued June 30, Myriad Genetics reports that tarenflurbil (Flurizan) failed to have a significant effect in a phase 3 trial of patients with mild Alzheimer's disease (AD). The failure of Flurizan™ is generally attributed to its insufficient pharmacodynamics, i.e., inadequate ability to penetrate the brain and engage its target protein at doses sufficient to yield an effect. Two additional Phase 3 trials were terminated and further development of Flurizan™ was discontinued. Separate clinical development of Flurizan™ for prostate cancer has also been discontinued following negative Phase 2 results. Tarenflurbil activates c-Jun N terminal kinase, increases AP-1 binding to DNA, and downregulates cyclin D1 expression, resulting in the arrest of tumour cells in the G1 phase of the cell cycle and apoptosis. This agent also affects the expression of nuclear factor kappa B, a rapid response transcription factor that stimulates the immune response to tumour cells. Tarenflurbil does not inhibit the enzyme cyclooxygenase. The Fraunhofer Institute for Molecular Biology and Applied Ecology is currently developing tarenflurbil for the treatment of relapsing, remitting multiple sclerosis.

CNS Activity

Curator's Comment: Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Only insufficient levels of tarenflurbil were able to cross the blood–brain barrier: Tarenflurbil only passes the blood–brain barrier at levels of 05–1.0%.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
307.0 µM [IC50]
Target ID: P18893
Gene ID: 16153.0
Gene Symbol: Il10
Target Organism: Mus musculus (Mouse)
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
20.3 μg/mL
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
38.6 μg/mL
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
45 μg/mL
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
173 μg × h/mL
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
465 μg × h/mL
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
546 μg × h/mL
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.17 h
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6.88 h
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.61 h
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TARENFLURBIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Overview

OverviewOther

Drug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Flurbiprofen does not change the bispectral index and 95% spectral edge frequency during total intravenous anaesthesia with propofol and fentanyl.
2002 Jul
Use of a wick to deliver preoperative mydriatics for cataract surgery.
2003 Nov
Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.
2004 Jan 9
The history of albuminous nephritis. 1840.
2005
Ambrosius Holbein's memento mori map for Sir Thomas More's Utopia. The meanings of a masterpiece of early sixteenth century graphic art.
2005 Jul 23
Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on propofol injection in the hand: a prospective, randomized, double-blind, vehicle-controlled, dose-finding study in Japanese adult surgical patients.
2005 May
Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium.
2006 Mar-Apr
[Clinical observation of propofol combined with flurbiprofen axetil for induced abortion anesthesia].
2006 Oct
Alzheimer's disease: progress in the development of anti-amyloid disease-modifying therapies.
2007 Feb
Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.
2007 Jul 24
[Effect of postoperative analgesia with flurbiprofen axetil and sufentanyl on metabolism of surgical patients with intestinal carcinoma].
2007 Oct
Therapeutic time window of flurbiprofen axetil's neuroprotective effect in a rat model of transient focal cerebral ischemia.
2008 Dec 20
Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, parallel-group, placebo-controlled study.
2008 Feb
Tarenflurbil protection from cytotoxicity is associated with an upregulation of neurotrophins.
2008 Nov
Subpopulations of neurons in visual area v2 perform differentiation and integration operations in space and time.
2009
Disease-modifying approach to the treatment of Alzheimer's disease: from alpha-secretase activators to gamma-secretase inhibitors and modulators.
2009
Late-life dementias: does this unyielding global challenge require a broader view?
2009 Dec 16
Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial.
2009 Dec 16
The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments.
2009 Jan
Alzheimer's disease therapeutic research: the path forward.
2009 Jul 9
Drug development for Alzheimer's disease: where are we now and where are we headed?
2009 Jun
NSAIDs: How they Work and their Prospects as Therapeutics in Alzheimer's Disease.
2010
Calcium signaling and neurodegeneration.
2010 Apr
Infertility caused by tubal blockage: An ayurvedic appraisal.
2010 Apr
Disease-modifying drug fails in Alzheimer's study.
2010 Apr
Can novel therapeutics halt the amyloid cascade?
2010 Apr 9
Drug development for Alzheimer's disease: recent progress.
2010 Dec
[Ion-sensitive nanoemulsion-in situ gel system for ophthalmic delivery of flurbiprofen axetil].
2010 Jan
[Drug therapy for Alzheimer's disease].
2010 Jul
Analgesic effect of parecoxib and flurbiprofen axetil for patients undergoing laparoscopic cholecystectomy and their influences on platelet aggregation.
2010 Jun
Update on the pharmacological treatment of Alzheimer's disease.
2010 Mar
[The effect of flurbiprofen axetil on laparoscopic cholecystectomy].
2010 Mar 23
[Population pharmacokinetic modeling of flurbiprofen].
2010 Nov
Prevention of pain with the injection of microemulsion propofol: a comparison of a combination of lidocaine and ketamine with lidocaine or ketamine alone.
2010 Oct
Specialization without the Hospital: The Case of British Sports Medicine.
2010 Oct
Are we prepared to deal with the Alzheimer's disease pandemic?
2010 Oct
Tarenflurbil in patients with mild Alzheimer's disease.
2010 Sep
γ-Secretase modulator in Alzheimer's disease: shifting the end.
2012
Patents

Patents

Sample Use Guides

Alzheimer's disease treatment: 800 mg tarenflurbil twice per day was well tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild AD.
Route of Administration: Oral
In vitro, Tarenflurbil inhibited Abeta42 secretion with IC(50) of 268 uM in a human neuroglioma cell line (H4) carrying the double Swedish mutation (K595N/M596L) of the human amyloid precursor protein (APPsw).
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:52:25 UTC 2023
Edited
by admin
on Sat Dec 16 17:52:25 UTC 2023
Record UNII
501W00OOWA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TARENFLURBIL
INN   MI   USAN  
INN   USAN  
Official Name English
FLURBIPROFEN, (R)-
Common Name English
MPC-7869
Code English
tarenflurbil [INN]
Common Name English
TARENFLURBIL [USAN]
Common Name English
R-FLURBIPROFEN
Common Name English
TARENFLURBIL [MI]
Common Name English
E-7869
Code English
Classification Tree Code System Code
NCI_THESAURUS C2189
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
NCI_THESAURUS C257
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID40199508
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
MERCK INDEX
m10466
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY Merck Index
WIKIPEDIA
TARENFLURBIL
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
ChEMBL
CHEMBL190083
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
INN
8417
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
USAN
NN-86
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
CAS
51543-40-9
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
CHEBI
38666
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
ECHA (EC/EINECS)
257-264-7
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
SMS_ID
300000034396
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
DRUG BANK
DB05289
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
PUBCHEM
92337
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
MESH
C505522
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
NCI_THESAURUS
C26666
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
FDA UNII
501W00OOWA
Created by admin on Sat Dec 16 17:52:26 UTC 2023 , Edited by admin on Sat Dec 16 17:52:26 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
RACEMATE -> ENANTIOMER
TARGET->MODULATOR
Related Record Type Details
ACTIVE MOIETY